Evaluation of Racial Differences in Cardiorespiratory Fitness Decline with Aging & Underlying Biological Mechanisms

项目摘要： 射血分数正常的心力衰竭（HF）常见于老年人， 普遍性。此外，HF（包括HFpEF）的负担存在很大的种族差异， 非裔美国人（AA）HF患病率远高于其他种族。在一系列的流行病学 研究，我们已经证明，低心肺功能（CRF），测量为峰值摄氧量 (peak最大负荷试验中的VO 2）是HF高风险的一个强有力的独立预测因子， HFpEF，老年人。此外，AA中的CRF水平始终低于其他 种族总之，低CRF和加速的与年龄相关的CRF下降可能是 HF负担的种族差异。更好地理解种族歧视的潜在机制 低CRF和年龄相关CRF下降的患病率差异是开发新的，有效的 预防老年AA患者HF的方法。因此，在这项研究中，我们的目的是评估种族 CRF年龄相关性下降的差异及其潜在的生物学机制。为此我们将 在达拉斯心脏研究（DHS）中进行一项巢式病例对照研究，DHS是一项多种族社区队列研究， 居住的个体，包括年龄、性别和风险因素（BMI、收缩压和舒张压）相匹配的老年AA和白色成人。 血压，糖尿病状态），在中年（平均年龄50-55岁）接受CRF检测，作为 DHS第2阶段访问（2007-09），并在10年后参加DHS第3阶段（2019-2022）。参与者 将接受重复CRF评估和全面的最先进表型分析， 评价CRF种族差异的潜在机制，包括：每搏输出量储备 通过超声心动图、心率储备、心肌灌注、心脏MRI的心肌能量学、骨骼 通过7 T MRI评估肌肉能量学，通过全身MRI评估局部脂肪组织。峰值vo 2 结合其中心和外周决定因素，将在匹配的AA和白色之间进行比较 参与DHS第三阶段的人员。成功完成这两个目标将量化AA中CRF的下降 与白色老年人的第一次，并阐明具体的机制，从而，提供关键的 深入了解低CRF的潜在病理生理机制。

Project Abstract: Heart failure (HF) with preserved ejection fraction (HFpEF) is common in older adults and increasing in prevalence. Furthermore, there are substantial racial disparities in the burden of HF, including HFpEF, such that African American (AA) have much higher prevalence of HF than other races. In a series of epidemiological studies, we have demonstrated that low cardiorespiratory fitness (CRF), measured as peak oxygen uptake (peak VO2) on a maximal stress test, is a strong independent predictor of higher risk of HF, particularly HFpEF, in older adults. Furthermore, CRF levels among AA are consistently lower as compared with other races. Taken together, low CRF and accelerated age-related decline in CRF may be key contributors to the racial differences in the burden of HF. A better understanding of the mechanisms underlying the racial disparities in prevalence of low CRF and age-related CRF decline is key to developing novel, effective approaches to prevention of HF in older AA adults. Accordingly, in this study, we aim to evaluate the racial differences in age-related decline in CRF and their underlying biological mechanisms. To this end, we will perform a nested case-control study within the Dallas Heart Study (DHS), a multi-ethnic cohort of community- dwelling individuals, including older AA and white adults matched for age, sex, and risk factors (BMI, systolic blood pressure, diabetes status) who underwent CRF testing in middle-age (mean age 50-55) as part of the DHS phase 2 visit (2007-09) and are participating in the DHS phase 3 10-years later (2019-2022). Participants will undergo repeat CRF assessment and comprehensive state-of-the-art phenotyping to comprehensively evaluate the potential mechanisms of racial differences in CRF, including the following: stroke volume reserve by echocardiogram, heart rate reserve, myocardial perfusion, myocardial energetics by cardiac MRI, skeletal muscle energetics assessment by 7T MRI, and regional adipose tissue by whole body MRI. Peak VO2 combined with its central and peripheral determinants will be compared among matched AA and white participants in the DHS phase 3. Successful completion of these two aims will quantify the CRF decline in AA versus white older individuals for the first time and elucidate specific mechanisms, thereby, providing critical insight into the underlying pathophysiologic mechanisms of low CRF.